CD8(+) cell noncytotoxic anti-human immunodeficiency virus response inhibits expression of viral RNA but not reverse transcription or provirus integration

CD8(+) T cells from human immunodeficiency virus (HIV)-infected individuals can suppress HIV replication in CD4(+) cells by a noncytotoxic mechanism t hat inhibits the expression of viral RNA. The present study examined whethe r other step(s) in the virus replicative cycle could be affected by the CD8 (+) cells. Culturing HIV-infected Ca4(+) T cells with antiviral CD8(+) T ce lls did not significantly reduce the amounts of (i) early HIV DNA reverse t ranscripts (detected by LTR-U3/R), (ii) total nuclear HIV gag DNA, or (iii) integrated proviral DNA, However, exposure to the CD8(+) T cells did cause a reduction in the amount of multiply spliced tat and full-length gag mRNA expressed by the infected CD4(+) T cells, confirming previous observations . The levels of glyceraldehyde-3-phosphate dehydrogenase and interleukin-2 receptor-alpha mRNA were not affected. The results support the conclusion t hat the noncytotoxic anti-HIV response of CD8(+) T cells, demonstrable in v itro, does not affect any of the virus replication steps leading to the int egration of proviral HIV, but specifically interrupts the expression of vir al RNA.